Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

NCT ID: NCT04335552

Last Updated: 2021-05-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-17
• Study Completion Date: 2020-06-26

Brief Summary

This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens:

Arm 1: Standard of care alone

Arm 2: Standard of care plus hydroxychloroquine

Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups:

1. Standard of care alone

2. Standard of care plus hydroxychloroquine

3. Standard of care plus azithromycin

4. Standard of care plus hydroxychloroquine plus azithromycin

Conditions

SARS-CoV-2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of care

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

Standard of care

Standard of care plus hydroxychloroquine

Standard of care plus hydroxychloroquine for 5 days

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

Standard of care

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5

Standard of care plus azithromycin

Standard of care plus azithromycin for 5 days

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

Standard of care

Azithromycin

Intervention Type: DRUG

Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5

Standard of care plus hydroxychloroquine plus azithromycin

Standard of care plus hydroxychloroquine plus azithromycin for 5 days

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

Standard of care

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5

Azithromycin

Intervention Type: DRUG

Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5

Interventions

Standard of care

Standard of care

Intervention Type: OTHER

Hydroxychloroquine

Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5

Intervention Type: DRUG

Azithromycin

Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR develop symptoms of COVID-19 during hospitalization

2. Subject (or legally authorized representative) can provide written informed consent (in English or Spanish) affirming intention to comply with planned study procedures prior to enrollment

3. Male or female adult aged 12 years or older at the time of enrollment

4. Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid amplification assay (public health or commercial) in any respiratory specimen collected within 14 days of randomization

5. Illness of any duration that includes

• Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR
• Clinical documentation of lower respiratory symptoms (cough, shortness of breath, wheezing) OR
• Any documented SpO2 ≤ 94% on room air OR
• Any inpatient initiation or supplemental oxygen regardless of documented cause

Exclusion Criteria

1. Participating in any other clinical trial of an experimental agent for COVID-19

2. On hydroxychloroquine at any time during hospitalization, or within 180 days of hospitalization for COVID-19 regardless of indication

3. History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any classification

4. Most recent ECG prior to time of screening with QTc of ≥500 msec

5. Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives

6. Death anticipated within 48 hours of enrollment

7. Inability to obtain informed consent from the patient or designated medical decision maker

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason Stout, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University Hospital

Locations

Duke Regional Hospital

Durham, North Carolina, United States

Duke University Hospital

Durham, North Carolina, United States

Durham VA Medical Center

Durham, North Carolina, United States

Duke Raleigh Hospital

Raleigh, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

PRO00105339

Identifier Type: -

Identifier Source: org_study_id